HHS Public Access Author manuscript Author Manuscript
J AIDS Clin Res. Author manuscript; available in PMC 2015 April 15. Published in final edited form as: J AIDS Clin Res. 2014 ; 5(6): 1000312–. doi:10.4172/2155-6113.1000312.
Polyamines: Predictive Biomarker for HIV-Associated Neurocognitive Disorders Salim Merali1,*, Carlos A. Barrero1, Ned C. Sacktor2, Norman J. Haughey3, Prasun K. Datta4, Dianne Langford4, and Kamel Khalili4,* 1Department
of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania, USA
Author Manuscript
2Department
of Neurology, Johns Hopkins Memory and Alzheimer’s Disease Treatment Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 3Department
of Neurology, Richard T Johnson Division of Neuroimmunology and Neurological Infections, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 4Department
of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
Abstract
Author Manuscript
Objectives—Spermidine/spermine-N1-acetytransferase (SSAT) is the key enzyme in the catabolism of polyamines that are involved in regulating NMDA functioning. Over expression of SSAT leads to abnormal metabolic cycling and may disrupt NMDA receptor signaling. In fact, the HIV protein Tat induces neurotoxicity involving polyamine/NMDA receptor interactions. Thus, we investigated abnormal polyamine cycling in HIV+ participants with varying degrees of HIVassociated neurocognitive disorders. Methods—Acetyl-polyamine (SSAT products) levels were assessed by HPLC in CSF from 99 HIV-infected participants (no cognitive impairment (NCI, n=25), asymptomatic neurocognitive impairment (ANI, n=25), mild cognitive and motor disorders (MCMD, n=24), and HIV-associated dementia (HAD, n=25)). Polyamine levels in brain tissues from a subset of participants (uninfected (n=3), NCI (n=3), and MNCD (n=3)) were also assessed. Human primary astrocytes expressing HIV Tat were assessed for levels of the SSAT activity.
Author Manuscript
Results—Activation of the polyamine catabolic enzyme, SSAT increases polyamine flux in brain and CSF of HIV infected individuals with HIV-associated neurocognitive disorders. CSF levels of acetylated polyamine increase with the degree of HAND severity as indicated by significantly increased acetylpolyamine levels in HAD participants compared to NCI and ANI (p
J AIDS Clin Res. Author manuscript; available in PMC 2015 April 15. Published in final edited form as: J AIDS Clin Res. 2014 ; 5(6): 1000312–. doi:10.4172/2155-6113.1000312.
Polyamines: Predictive Biomarker for HIV-Associated Neurocognitive Disorders Salim Merali1,*, Carlos A. Barrero1, Ned C. Sacktor2, Norman J. Haughey3, Prasun K. Datta4, Dianne Langford4, and Kamel Khalili4,* 1Department
of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania, USA
Author Manuscript
2Department
of Neurology, Johns Hopkins Memory and Alzheimer’s Disease Treatment Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 3Department
of Neurology, Richard T Johnson Division of Neuroimmunology and Neurological Infections, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 4Department
of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
Abstract
Author Manuscript
Objectives—Spermidine/spermine-N1-acetytransferase (SSAT) is the key enzyme in the catabolism of polyamines that are involved in regulating NMDA functioning. Over expression of SSAT leads to abnormal metabolic cycling and may disrupt NMDA receptor signaling. In fact, the HIV protein Tat induces neurotoxicity involving polyamine/NMDA receptor interactions. Thus, we investigated abnormal polyamine cycling in HIV+ participants with varying degrees of HIVassociated neurocognitive disorders. Methods—Acetyl-polyamine (SSAT products) levels were assessed by HPLC in CSF from 99 HIV-infected participants (no cognitive impairment (NCI, n=25), asymptomatic neurocognitive impairment (ANI, n=25), mild cognitive and motor disorders (MCMD, n=24), and HIV-associated dementia (HAD, n=25)). Polyamine levels in brain tissues from a subset of participants (uninfected (n=3), NCI (n=3), and MNCD (n=3)) were also assessed. Human primary astrocytes expressing HIV Tat were assessed for levels of the SSAT activity.
Author Manuscript
Results—Activation of the polyamine catabolic enzyme, SSAT increases polyamine flux in brain and CSF of HIV infected individuals with HIV-associated neurocognitive disorders. CSF levels of acetylated polyamine increase with the degree of HAND severity as indicated by significantly increased acetylpolyamine levels in HAD participants compared to NCI and ANI (p
